D
FIELD IONIZATION AND FIELD DESORPTION MASS SPECTROMETRY: PAST, PRESENT, AND FUTURE
Robert P. Lattimer The BFGoodrich Research and Development Center Brecksville, OH 44141
Harts-Rolf Schulten Department of Trace Analysis Fachhochschule Fresenius D-6200 Wiesbaden Federal Republic of Germany
In the past several years, a number of new ionization methods in mass spec trometry (MS) have been introduced. These new techniques have extended mass spectrometric analysis to a wide variety of labile (thermally unstable), highly polar, and high molecular weight materials. Field ionization (FI) and field desorption (FD) MS are two of the pioneering techniques in this ar senal of alternative ionization meth ods. FI-MS, which was introduced for organic molecules in 1954, was the first soft ionization method. (Soft ionization refers to processes that produce high relative abundances of molecular, or quasimolecular, ions.) FD-MS, which was invented in 1969, was the first de sorption ionization method. (Desorp tion ionization refers to processes that produce ions directly from the solid or liquid state.) FI-MS and FD-MS have a number of useful features, including very high 0003-2700/89/A361-1201 /$01.50/0 © 1989 American Chemical Society
molecular ion abundances, higher mass capability, and applicability to a wide variety of compound types. In this R E P O R T , we will give an overview of the current status of FI-MS and FDMS methods, including results from a recent survey of FI-MS and FD-MS users. After reading about some of the unique features and applications of these methods, we hope that potential users may consider using FI-MS and FD-MS. Readers interested in more detailed explanations of FI/FD-MS theory, procedures, and applications are referred to various reviews on the subject (1-7). Evolution of FI-MS and FD-MS
The invention of field ion microscopy by E. W. Mueller (8) initiated several fields of study, including FI/FD-MS. In 1954, M. G. Inghram and R. Gomer at the University of Chicago described the attachment of an FI microscope to a mass spectrometer (9,10). They were thus able to generate mass spectra from a number of small molecules, including hydrogen, oxygen, and ethane. In 1957, H. D. Beckey at the University of Bonn began a systematic investigation of FIMS. His research focused on the mass spectrometric applications of the tech nique, and he made many fundamental discoveries in the areas of kinetics and mechanisms of gas-phase organic reac
tions and the use of FI/FD-MS for or ganic chemical structure analysis. Beckey and co-workers made several major contributions to our understand ing and practice of FI/FD-MS, includ ing the first focusing FI source (1958), field dissociation studies of organic molecular ions (1961), field ionization kinetics of gas-phase decomposition of organic ions (1961), the use of thin
REPORT wires as field emitters (1963), the de velopment of activated carbon micro needle emitters (1968), and the inven tion of field desorption (1969). The first commercial F I / Ε Ι ion source was introduced for magnetic sector instruments by MAT (Bremen, FRG) in 1967 (11, 12). The emitter could be retracted for EI operation, but the system had to be vented to change the emitter. The first commercial FD/FI/EI ion source, with the emitter on a sliding pushrod probe, was intro duced by Varian MAT in 1973. This provided a marked improvement, be cause the emitter could easily be re placed or loaded with sample without venting the system. Today all of the major magnetic sector manufacturers
ANALYTICAL CHEMISTRY, VOL. 61, NO. 21, NOVEMBER 1, 1989 · 1201 A
REPORT offer FI/FD sources as accessories for their instruments. A search of Chemical Abstracts for FI/FD-MS articles published between 1954 and 1988 revealed more than 1200 articles that dealt essentially with FI/FD-MS applications in organic mass spectrometry (Figure 1). The number of FI/FD-MS publications rose rapidly in the early to mid-1970s, reaching a peak in 1978. A noticeable
FI/FD-MS User Survey Throughout this REPORT we have included results from a sur vey of FI/FD-MS users conduct ed between December 1988 and April 1989. Our mailing list for this survey consisted primarily of authors who published articles on FI-MS or FD-MS from 1979 to 1988. A few other scientists were included that we knew had FI/FD ion sources but had not published in the open literature. The survey was sent to 212 re searchers representing 180 sepa rate institutions, and survey forms from 74 of these institu tions were returned. The average respondent had 12 years of FI/ FD-MS experience. We asked users which instru ments they used for FI/FD-MS analysis. We found that the major ity of FI/FD-MS work is per formed using double-focusing magnetic systems, most often from Varian/Finnigan MAT (39%), JEOL (20%), VG (18%), Kratos/ ΑΕΙ (10%), and Hitachi (4%). We also asked the users what percentage of total instrument time (including all ionization methods) in their laboratories is devoted to FI/FD-MS analysis. According to the survey respons es, the typical user devotes 21% of instrument time to FD-MS and 9% to FI-MS. Also, 63% of these users do little or no FI-MS, and 27% do essentially no FDMS work. It is interesting to note that more than a fifth (22%) of these mass spectrometrists (all of whom have FI/FD sources) re port that they currently perform essentially no FI-MS or FD-MS analysis. Some of these scientists (particularly those engaged in biochemical analysis) are former users of FD-MS who have largely replaced the technique with FAB-MS.
drop occurred after 1983 because of the advent and popularity of fast atom bombardment mass spectrometry (FAB-MS) and (to a lesser extent) oth er new desorption ionization tech niques. The number of publications on FI/FD-MS has remained stable at ap proximately 40 per year since 1984. In nearly a third (32%) of the articles found in our literature search, the pri mary author was from West Germany; this is not surprising in view of the ear ly development of FI/FD-MS in Bonn. Authors from the United States con tributed 14% of the articles, and Japa nese authors accounted for 13%. Other countries of origin included the U.S.S.R. (9%), the United Kingdom
(6%), Canada (3%), The Netherlands (2%), and Australia (2%). Principles and procedures
The principles involved in FI/FD-MS are fundamentally different from those for methods that rely on electron, ion, atom, particle, or laser beams for ion ization. A simple diagram of a combi nation FD/FI ion source is shown in Figure 2. The field emitter consists of a thin (usually 10 μιη) tungsten wire that is supported on two metal posts with a ceramic base. The emitter is on a slid ing pushrod probe, which can be re moved from the ion source for sample loading or emitter replacement. The emitter wire is covered with micro-
fear Figure 1 .
FI/FD-MS publications by year.
Extraction plate (counter electrode)
Field probe
ο ο
° ρ
ο
°
\
> Field emitter
Figure 2.
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Diagram of an FD/FI ion source.
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To analyzer Μ + ·, MH+
REPORT
Figure 3.
Photomicrograph of a carbon microneedle emitter.
Figure 4.
FD mass spectrum of 2,2,4-trimethyl-1,2-dihydroquinoline dimer.
(Adapted with permission from Reference 13.)
needles of pyrolytic carbon or silicon (Figure 3). The emitter is held at the accelerating potential, and the wire is situated within a few millimeters of a counter electrode (or extraction plate), which is held at a potential 8-12 kV lower than that of the emitter. The high field strengths necessary for field ionization (10 7 -10 8 V/cm) are present near the tips of the microneedles. Field ionization involves the removal of electrons from a species by quantum mechanical tunneling in a high electric field. In practice, FI-MS refers to the technique in which the sample to be analyzed is introduced as a vapor using a heatable direct probe, heated batch inlet, or GC/MS interface. Field desorption refers to the technique in which the sample is deposited directly on the emitter before it is inserted into the ion source. This is an ambiguous term, because it implies that it is the electric field that causes desorption and ionization of the ana-
lyte from the probe. It is well known, however, that the field is only one factor in the process; "field ionization" is only one of several ionization processes that may occur. Thus, most mass spectrometrists use the term "field desorption" to refer to the sample introduction technique and not necessarily to the method of ionization. The term is firmly ingrained in the literature, however, and no suitable alternative term has been proposed. In our survey, 86% of the respondents said that they use carbon microneedle emitters and 11% silicon emitters. Silicon emitters can be manufactured more rapidly, but carbon emitters are more rugged and can be heated to much higher temperatures. Only a few respondents (3%) reported the use of other types of emitters (bare wire, metal microneedles, metal tip, razor blade, or volcano). About two-thirds (66%) of the respondents said that they make their own emitters. (Emitter
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preparation devices are available from mass spectrometer manufacturers as well as independent suppliers.) Other users purchase their emitters either from mass spectrometer manufacturers (15%) or from independent vendors (19%). The choice of making or buying emitters usually comes down to cost and time. Many universities make their own emitters because they have a ready source of inexpensive labor (students), whereas many industrial laboratories find it more cost-effective to purchase emitters. For FD-MS analysis, the emitter must be loaded with sample. The first step is to dissolve the material to be analyzed in a suitable solvent (preferably a volatile one such as acetone or dichloromethane). If dissolution is not possible, suspension with sonification may be sufficient. The emitter is then dipped into the analyte solution or the solution is dripped onto the wire. The dipping technique is a little faster, but the syringe technique should be used when the amount of available sample is very small or when careful control of sample amount and position on the wire is necessary (as in quantitative work). Microsyringe manipulators can be made (or purchased commercially) if the ultimate in sample loading care and convenience is desired. In our survey, 66% of the respondents said that they use syringe deposition, and 33% use the dipping technique. Other emitter loading methods (e.g., aerosol deposition and freeze loading) are used only infrequently. Ion formation mechanisms Part of the versatility of the FI-MS and FD-MS methods comes from the variety of ionization mechanisms that can be observed with different analytes. The four most commonly observed mechanisms are field ionization, cation attachment, thermal ionization, and proton abstraction. Field ionization. Field ionization is the first mechanism that mass spectrometrists think of when considering FI/FD-MS, but it is only one of several possibilities. As stated earlier, field ionization is the removal of electrons from a species by quantum mechanical tunneling in a high electric field. This leads to the production of molecular ions (M + ' in positive ion mode), and this mechanism of ionization is generally observed for nonpolar or slightly polar organic compounds. The dimer of 2,2,4-trimethyl-l,2-dihydroquinoline (TMDQ) is a typical example for this ionization method (13). Figure 4 shows the FD mass spectrum of TMDQ dimer taken with no heating current applied to the emitter.
REPORT This is a typical single-peak FD mass spectrum that is appealing to many or ganic chemists. The spectrum immedi ately confirms (or establishes) the mo lecular weight of the analyte and tells something about the purity of the ma terial. In the case of mixtures, one peak is normally observed for each compo nent; therefore, FI-MS or FD-MS can be used as a screening technique for complex samples. Cation attachment. Cation attach ment is also called cationization or desolvation. In this process, cations (typi cally H + or Na + ) attach themselves to receptive sites on analyte molecules in the condensed phase; the combination of emitter heating and high field re sults in the desorption of cation attach ment ions (e.g., MNa + ). This mecha nism is typically observed for more po lar organic molecules (e.g., ones with aliphatic hydroxyl or amino groups). The spectrum of azathioprine (Fig ure 5) is a typical example of this ion ization method (14). Figure 5a shows the FD mass spectrum taken at 22 mA emitter heating current (EHC), which for this molecule corresponds to the best anode temperature (BAT). The BAT is the temperature at which the intensity of the molecular ion is maxi mal and that of the fragment ions is minimal. As the emitter is heated, the BAT occurs shortly after the point at which molecular ions begin to form. Figure 5b shows the spectrum of aza thioprine at a temperature somewhat higher than the BAT. In many mole cules (depending upon the chemical structure), an increase of heating above the BAT will induce fragmentation, which may be desirable for chemical structure analysis. FI/FD fragmenta tion is normally characterized by the presence of only a few ions, all of which are clearly defined. This differs mark edly, for example, from the "peak at every mass" phenomenon commonly observed in FAB-MS. Thermal ionization. Thermal ion ization of preformed ions may be ob served for organic and inorganic salts, for which the field lowers the desorp tion temperature, facilitates focusing, and enhances the ion current. The emitter is used as a "solids probe" to hold and heat the sample. A typical example for an organic salt, tetramethylammonium iodide, is shown in Figure 6 (15). The spectrum was collected using a bare tungsten wire emitter, and the tetramethylam monium cation (m/z 74) is the base peak. The weak ion at m/z 275 is a cluster ion consisting of two cations plus an anion (C2A+). Cluster ions are frequently observed in the FD-MS (or thermal ionization MS) of salts.
Proton abstraction. Proton ab straction is a common ion formation mechanism in the negative ion (NI) FD-MS mode. It is not often reported in the literature because little NI-FDMS work is done. (Field electron emis sion has to be contended with in NIFD-MS.) Polar organics in the NI
Figure 5.
mode will often show (M — H)~ ions. A typical example is shown in Figure 7 and is taken from work done by Roellgen (16), who has made numerous con tributions in the area of NI-FD-MS ap plications. The first three ionization mecha nisms discussed here all have their ana-
FD mass spectra of azathioprine.
(a) 22 mA emitter heating current (equal to the BAT) and (b) 25 mA EHC (greater than the BAT). Spectra have been transcribed from photoplates; some isotope peaks are omitted. (Adapted with permission from Reference 14.)
Figure 6. FD mass spectrum of tetramethylammonium iodide using a bare 10-μιη tungsten wire emitter. (Adapted with permission from Reference 15.)
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REPORT logues in NI-FD-MS (5). Molecular an ions (M~) can be produced through field ionization. Anion attachment oc curs for some molecules to yield, for example, (M + Cl)~. Salts generally yield anion (A~) and cluster ion (e.g., CA2 - ) spectra via thermal desorption. Advantages
The principal advantages of FI-MS and FD-MS include high molecular ion abundances, fairly high mass capabili ty, applicability to a wide variety of compound types, and availability on general-purpose organic mass spectro meters. High molecular ion abundances. At or near the BAT, most organic com pounds will produce intense ions in the molecular ion region (M + ', M H + , MNa + ) with few fragment ions or none at all. FI-MS and FD-MS are therefore excellent for molecular weight determi nation. For "pure" materials, a qualita tive assessment of purity level can be made. Mixtures can be screened to as sess the number of components and their approximate relative abun dances. Chemical structures can often be elucidated from just the molecular weights of the components plus a knowledge of the chemistry and history of the sample. Fairly high mass capability. As with most ionization methods, FI and FD mass spectra are most often ac quired for compounds of mass
